Gene therapy is life-changing for children with a life-threatening brain disorder

If you have never heard of AADC deficiency count yourself lucky. It’s a rare, incurable condition that affects only around 135 children worldwide but it’s impact on those children and their families is devastating. The children can’t speak, can’t feed themselves or hold up their head, they have severe mood swings and often suffer from insomnia.

But Dr. Krystof Bankiewicz, a doctor and researcher at the University of California San Francisco (UCSF), is using techniques he developed treating Parkinson’s disease to help those children. Full disclosure here, CIRM is funding Dr. Bankiewicz’s Parkinson’s clinical trial.

In AADC deficiency the children lack a critical enzyme that helps the brain make serotonin and dopamine, so called “chemical messengers” that help the cells in the brain communicate with each other. In his AADC clinical trial Dr. Bankiewicz and his team created a tiny opening in the skull and then inserted a functional copy of the AADC gene into two regions of the brain thought to have most benefit – the substantia nigra and ventral tegmental area of the brainstem.

Image showing target areas for AADC gene insertion: Courtesy UCSF

When the clinical trial began none of the seven children were able to sit up on their own, only two had any ability to control their head movement and just one could grasp an object in their hands. Six of the seven were described as moody or irritable and six suffered from insomnia.

In a news release Dr. Bankiewicz says the impact of the gene therapy was quite impressive: “Remarkably, these episodes were the first to disappear and they never returned. In the months that followed, many patients experienced life-changing improvements. Not only did they begin laughing and have improved mood, but some were able to start speaking and even walking.”

Those weren’t the only improvements, at the end of one year:

  • All seven children had better control of their head and body.
  • Four of the children were able to sit up by themselves.
  • Three patients could grasp and hold objects.
  • Two were able to walk with some support.

Two and a half years after the surgery:

  • One child was able to walk without any support.
  • One child could speak with a vocabulary of 50 words.
  • One child could communicate using an assistive device.

The parents also reported big improvements in mood and ability to sleep.

UCSF posted some videos of the children before and after the surgery and you can see for yourself the big difference in the children. It’s not a cure, but for families that had nothing in the past, it is a true gift.

The study is published in the journal Nature Communications.

6 thoughts on “Gene therapy is life-changing for children with a life-threatening brain disorder

    • Sorry Melissa, we don’t do any research, we just fund it. And I don’t know of any researcher who is currently taking out genes.

  1. AADC deficiency is one of genetic disorders caused by changes or mutation in DDC gene. The gene is critical to express AADC enzyme and provide instructions to the body for functioning. DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters called dopamine and serotonin.

    Results of gene therapy in children with deficiency of AADC enzyme showed that an improvement of at least one action among the children after treatment, such as better control of head and body movements, sitting up, reading and so on. The disporpotional of neurons transfected with functional gene of AADC in two regions brainstem caused both substantia nigra and ventral degmental developed suboptimum of health in children. The inefficiency of gene therapy to transduce 100% of neurons caused partially recovery of children from their illnesses. In addition, children with different age groups have different requirement of dosages for transfected neurons with AADC to gain optimum health. However, the promoter of most viral carriers have lost ability to control the expression levels of AADC enzyme for requirement of each individual.

    This is in contrast to the patients with Parkinson’s disease (PD), the damage or death of nerve cells or neurons in substantia nigra of brain trigger low dopamine secretion and cause them experience the movement related problems. It is uncertain the key factors to cause PD but genetics and environmental factors are likelihood to induce PD in people. Most people develop disorder are over age of 50. Thus, age is considered the greatest risk factor to develop PD. In reviewing the life cycle of humans which can be divided into 5 stages of development, these include infant, puberty, adolescent, menopause and elderly. The endocrine system release variety of growth factors and hormones to regulate entire of life for humans to grow. Evidence proved that all cells require growth factors and hormones for proliferation, differentiation, behavior and survival. Therefore, the regulation of endocrine system becoming subsides during people approaching old age. The lack of growth factors cause the integrity of cell loss and genetic of cell easily to mutate, neurons become highly susceptibility to pollutants and loss affinity of growth factor receptors on neurons of brain might be the risk factors to induce PD in man. iPSCs technology to develop stem cells therapy for old generation may not be rewarded unless prior treatment of cells to turn around the unhealthy into healthy cells.

  2. Fantastic progress. We need to push this technology and innovate as much as we can, to improve the lives of children and adults alike.

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